A recently developed drug holds great promise for some children with acute lymphoblastic leukemia.

A recently developed drug, already used safely in adult leukemia clinical trials, holds great promise for some children with an aggressive form of cancer known as acute lymphoblastic leukemia (ALL). The findings were published in Blood (2015; doi:10.1182/blood-2014-12-618900).

The drug PR-104 was found to be effective against preclinical, laboratory models of aggressive T-lineage ALL (T-ALL). The research was led by Richard Lock, PhD, and Donya Moradi Manesh, PhD, both from the Children's Cancer Institute in Sydney, Australia.

The research team tested PR-104 through the Pediatric Preclinical Testing Program, a consortium funded by the US National Cancer Institute (NCI) to prioritize and fast track new drugs into clinical trials in children with aggressive cancers. Children's Cancer Institute is the only testing site located outside of the United States, and conducts all consortium's testing against childhood ALL.

"During the 10 years we've been funded under the NCI program, we've tested over 70 drugs and combinations, and PR-104 is one of the most exciting yet, with the potential to be fast-tracked into clinical trials for children," said Lock.

"We were so encouraged by our first results with PR-104 that we undertook additional studies which showed the drug to be preferentially active against T-ALL, a subtype of ALL affecting white blood cells known as 'T cells'.

"Around 15% of acute lymphoblastic leukemia patients have T-ALL, while 85% have a disease that affects their 'B cells', another white blood cell type. PR-104 is much less effective against these B cell leukemias.”

Lock explained that they believe that PR-104 might be an effective drug for patients who have initially benefited from conventional treatment for T-ALL, but who have subsequently relapsed.

Though they were baffled at first by why T-ALL responded to PR-104, the researchers realized that only the T cell subtype expressed high levels of AKR1C3, an enzyme that activates PR-104. The research team is in the process of examining the molecular biology behind AKR1C3, and trying to understand why T-ALL cells express very high levels of the enzyme.

"If we can work out what activates this enzyme in T cells, we might find a way of activating it in B cells, making the B cell disease sensitive to the drug as well," said Lock.

"Obviously it would be ideal if we could extend this drug's reach to include all acute lymphoblastic leukemia patients. In the meantime, we can envisage using PR-104 to target highly aggressive T-ALLs that express high levels of AKR1C3.”

Lock stated that they are actively pursuing opportunities to conduct a clinical trial to treat childhood T-ALL with PR-104.